SPHINX31 is a potent inhibitor of serine/arginine-rich protein kinase 1 (SRPK1) with IC50 of 5.9 nM. SPHINX31 inhibits phosphorylation of serine/arginine-rich splicing factor 1 (SRSF1). SPHINX31 treatment results in inhibition of SRSF1 phosphorylation at 300 nM in PC3 prostate cancer cells. Metabolic stability in mouse liver microsomes shows that SPHINX31 had medium clearance with a T1/2 of 95.79 min.
In vivo, SPHINX31 exerts a dose dependent inhibition of choroidal neovascularisation in mouse model. SPHINX31 inhibits blood vessel growth and macrophage infiltration. SPHINX31 treatment prolongs survival of immunocompromised mice transplanted with MLL-rearranged AML cells.
| Cell Experiment | |
|---|---|
| Cell lines | THP-1 cells |
| Preparation method | For synergy studies between SPHINX31 and iBET, THP-1 cells were seeded in 96-well plates at 10,000 cells per well and treated with SPHINX31 (dose range of 0.039–5 μM) and iBET (dose range of 9.8–312.5 nM) in an 8 by 6 matrix. Each treatment was carried out in triplicate. Cells were treated for 72 h, and cell viability was determined using CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay (Promega) in order to calculate the relative cell proliferation. Cell viability for each treatment was normalized against the DMSO control group. A Bliss independence model was employed to evaluate combination effects and calculate the Bliss independence score. All the compounds were dissolved in DMSO. |
| Concentrations | 0.039-5 μM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | DBA2J mice |
| Formulation | dissolved in 20%(w/v) 2-hydroxyproply beta-cyclodextrin vehicle |
| Dosages | 0.8 mg/kg |
| Administration | i.p. |
| Molecular Weight | 507.51 |
| Formula | C27H24F3N5O2 |
| CAS Number | 1818389-84-2 |
| Solubility (25°C) | DMSO 18 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related SRPK Products |
|---|
| MSC-1186
MSC-1186 is a highly selective pan-SRPK inhibitor with activity against SRPK1, SRPK2, and SRPK3 with IC50 values of 2.7 nM, 81 nM, and 0.6 nM, respectively.MSC-1186 can be used in cancer research. |
| SRPKIN-1
SRPKIN-1 is a covalent and irreversible SRPK1/2 inhibitor with IC50s of 35.6 and 98 nM, respectively. Anti-angiogenesis effect. |
| WAY-652848
WAY-652848 is a selective inhibitor of SRPK1 with an IC50 value of 0.58 μM.WAY-652848 effectively reduces choroidal neovascularization (CNV) in vivo, and can be used in the study of age-related macular degeneration. |
| SRPIN340
SRPIN340 is a selective SRPK inhibitor with Ki of 0.89 μM for SRPK1, showing no significant inhibitory activity against more than 140 other kinases. |
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